Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors

This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with SC-CAR4BRAIN, an autologous CD4+ and CD8+ T cells lentivirally transduced to express to express combinations of B7-H3, EGFR806, HER2, and IL13-zetakine chimeric antigen receptors (CAR). CAR T cells are delivered via an indwelling catheter into the ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors. A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into their ventricular system, and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that target B7H3, EGFR806, HER2, and IL13-zetakine on tumor cells. Patients will be assigned to 1 of 2 treatment Arms based on the type of their tumor: * Arm A is for patients with DIPG (meaning primary disease localized to the pons, metastatic disease is allowed) anytime after standard radiation OR after progression. * Arm B is for patients with non-pontine DMG (meaning DMG in other parts of the brain such as the thalamus or spine) anytime after standard radiation OR after progression. This Arm also includes other recurrent/refractory CNS tumors.

NCT Number	NCT05768880
Lead Sponsor	Seattle Children's Hospital
Conditions	Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, Recurrent CNS Tumor, Adult, Recurrent, CNS Tumor, Childhood, Refractory Primary Malignant Central Nervous System Neoplasm
Enrollment	72 participants
Start Date	2023-05-05
Primary Completion	2028-01-15 (estimated)
Study Completion	2043-12-31 (estimated)
Updated on ClinicalTrials.gov	2025-11-20